Underdrain for filtration membrane

ABSTRACT

A device and method for removal of liquid from the downstream side of a membrane or a well, such as a well of a multiwell plate. More specifically, the present invention is directed to a wicking structure, which channels droplets of liquid away from a membrane in communication with a plurality of wells. In the preferred embodiment, the wicking structure is placed in a manifold.

This application is a divisional of U.S. Ser. No. 09/565,963 filed May5, 2000, the disclosure of which is incorporated herein by reference.

BACKGROUND OF THE INVENTION

Test plates for chemical or biochemical analysis which contain aplurality of individual wells or reaction chambers are well knownlaboratory tools. Such devices have been employed for a broad variety ofpurposes and assays, and are exemplified in U.S. Pat. Nos. 4,734,192 and5,009,780, for example. Microporous membrane filters and filtrationdevices containing the same have become especially useful with many ofthe recently developed cell and tissue culture techniques and assays,especially in the fields of virology and immunology. Multiwell plates,used in assays, often use a vacuum applied to the underside of themembrane as the driving force to generate fluid flow through themembrane.

Typically, a 96-well filtration plate is used to conduct multiple assayssimultaneously. In the case of multiwell products, there is a need todeal with liquid collection, removal and recovery in an effectivemanner. In particular, high throughput applications, such as DNAsequencing, PCR product cleanup, plasmid preparation, drug screening andsample binding and elution require products that perform consistentlyand effectively. If droplets are allowed to remain in proximity to thepurified sample for longer than necessary, a variety of deleteriouseffects may result, including possible contamination of purified sample.

One such filtration device commercially available from MilliporeCorporation under the name “Multiscreen” is a 96-well filter plate thatcan be loaded with adsorptive materials, filter materials or particles.The Multiscreen underdrain has a phobic spray applied in order tofacilitate the release of droplets. More specifically, the MultiScreenincludes an underdrain system that includes a spout for filtratecollection. This spout not only directs the droplets but also controlsthe size of the drops. Without the underdrain system, very large dropsform across the entire underside of the membrane. The drop volume thatcan remain without such an underdrain is much larger than with such anunderdrain. The spout is hydrophobically treated to enhance dropletrelease for quantitative collection.

It would therefore be desirable to provide an effective means for liquidcollection in sample preparation devices such as multiwell arrays.

It would also be desirable to provide an effective means for removal offiltrate droplets from the underside of a membrane without requiring theaddition of an underdrain system.

SUMMARY OF THE INVENTION

The problems of the prior art have been overcome by the presentinvention, which provides a device and method for removal of liquid fromthe downstream side of a membrane or a well, such as a well of amultiwell plate. More specifically, the present invention is directed toa wicking structure, which channels droplets of liquid away from amembrane or well, preferably a plurality of wells. In the preferredembodiment, the wicking structure is placed in a vacuum manifold inclose proximity to the underside of the membrane or it can be anintegral part of the manifold.

Since the presence of the wicking structure below the downstream side ofthe membrane effectively removes droplets of filtrate, contaminants inthese droplets are channeled away from the membrane and are less likelyto re-contaminate the sample through diffusion or osmotic forces, forexample. Contamination of associated equipment, such as the robotic deckthat the samples are processed on, is also less likely or eliminated. Inaddition, a wicking structure makes successive washes of samples on theupstream side of the membrane more efficient since contaminants aredirected away from the underside of the membrane. The wicking structureis preferably used where quantitative collection of filtrate is notdesired.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 a is a schematic view of a conventional multi-well plate andmanifold after filtration as taken place;

FIG. 1 b is a schematic view of a multi-well plate and manifold with awicking matrix during filtration in accordance with the presentinvention;

FIG. 1 c is a schematic view of a multi-well plate and manifold with awicking matrix after filtration in accordance with the presentinvention;

FIG. 2 a is a schematic view of a multi-well plate and manifold duringfiltration, wherein the wick is an integral part of the manifold, inaccordance with another embodiment of the present invention; and

FIG. 2 b is a schematic view of a multi-well plate and manifold afterfiltration, where the wick is an integral part of the manifold, inaccordance with the embodiment of FIG. 2 a.

DETAILED DESCRIPTION OF THE INVENTION

Turning first to FIG. 1 a, there is shown a conventional plate andmanifold assembly. Plate 10 includes a plurality of wells 12 to which issealed a membrane 11, such as by heat-sealing, sealing with ultrasonics,solvents, adhesives, by diffusion bonding, etc. The type of membranesuitable is not particularly limited, and can include nitrocellulose,cellulose acetate, polycarbonate, polypropylene and polyvinylidenefluoride microporous membranes, or ultrafiltration membranes such asthose made from polysulfone, polyvinylidene fluoride, cellulose or thelike. A single membrane could be used, or where the sample preparationdevice is a plurality of wells, each well can contain or be incommunication with its own membrane which can be the same or differentfrom the membrane in communication with one or more of the other wells.The plate 10 is attached to a manifold 15, which includes a collectionreservoir for collecting filtrate 14. The drive source for thefiltration can be a vacuum source (not shown) connected via port 16. Apositive pressure source (not shown) also could be used as the drivingforce, and would be applied to the liquid head above the filter.

A liquid droplet 17 is shown extending from the membrane 11. Removal ofthis liquid droplet 17 from the downstream side of the membrane 11 isdesired to prevent contamination of other samples in the array as wellas to prevent contamination of the robotic deck that these samples areprocessed on.

FIG. 1 b illustrates a similar device with the wicking structure 20 ofthe present invention in place. The device is shown during thefiltration process. Thus, sample to be filtered 21 is in the wells 12′,and flows through the membrane 11′ due to the action of gravity, apositive pressure source, and/or a vacuum source in communication withport 16′. As a liquid droplet 17′ of filtrate forms, it contacts thewicking structure 20, is drawn by the wicking structure 20, and istherefore removed out of contact with the downstream side of membrane11′. The filtrate is then generally discarded.

FIG. 1 c shows the device of FIG. 1 b after filtration is complete. Few,if any droplets remain on membrane 11′. Filtrate 14′ seeps or is pulledby the vacuum from wicking structure 20 into the filtrate chamber, andcan be discarded or reused, depending upon the application.

The wicking structure 20 is a conduit for the liquid to be drawn off themembrane and directed away from the membrane. In a preferred embodiment,the wicking structure 20 is an absorbent material or matrix such asabsorbent elastomeric, cellulosic or plastic material, including paperand nonwoven materials. One particularly suitable material is ScotchBrite™. The wicking structure 20 can also be a non-absorptive materialsuch as a metal rib positioned below the membrane. The structure 20 canbe permanently positioned in the device, or can be removable forcleaning and reuse, for elution, or it can be disposable. The wickingstructure 20 also could be layers of the same or different absorbentmaterial.

Where the wicking structure or matrix 20 is not in contact with themembrane surface, the gap between the wicking structure 20 and themembrane 11′, must be sufficiently small to allow contact between thedroplets of filtrate passing through the membrane 11′ and the structure20. Those skilled in the art will be able to readily determine thesuitable positioning of the wicking structure 20, depending in part onthe volume of sample being used and the surface tension of that sample.For example, in applications such as PCR where the total array volume isvery small (10-100 μm), the wicking structure 20 and the underside ofthe membrane 11′ must be in close proximity so that even the smallestvolumes release from the membrane 11′. A suitable gap for thisapplication is 0.5 mm, which ensures no migration of contaminantsbecause the liquid is preferentially pulled into the structure 20leaving an air gap. In some applications, the wicking structure 20 cancontact the membrane 11′, resulting in a gap of zero.

The configuration of the wicking structure 20 is not particularlylimited. FIG. 2A shows an embodiment wherein the wicking structure 20′is an array of spaced ribs 30 positioned in the collection chamber ofthe manifold 15′. The ribs 30 extend in a direction from the collectionchamber towards the membrane, and can taper towards their free end asshown. The ribs 30 contact the droplets 17′ of liquid and direct themaway from the membrane 11′ and into the collection chamber (as filtrate14′) as shown in FIG. 2B. Preferably each rib 30 is positioned under thecenter of a well 12, and has a depth of greater than 1 mm.

In order to facilitate transfer of the droplet of filtrate from thesurface of the membrane 11′ to the wicking structure 20, 20′, themembrane 11′ can be rendered hydrophobic such as by treatment with ahydrophobic material such as a spray or the like. This helps isolate thedroplets from one another, thereby producing a more consistent point ofcontact with the support, and yielding a release of the droplets to themore hydrophilic surface of the wicking structure 20, 20′ leaving lessresidue on the membrane.

Regardless of the particular wicking structure used, the wickingstructure functions to remove droplets formed from a plurality of samplewells into a single or common collection chamber. Segregation of thedroplets forming from each well, and thus quantitative collection of thefiltrate, is not required; droplets from all of the wells can becombined and collected together. The particular configuration of thecommon collection chamber is not particularly limited.

1. A method of filtering a liquid sample contained in a plurality ofsample reservoirs, comprising: causing said sample to pass through amembrane in communication with each of said plurality of samplereservoirs to form a plurality of respective filtrates, said membranehaving a membrane surface, each of said plurality of respectivefiltrates forming at least one droplet on said membrane surface;directing each of said at least one droplet from said membrane surfaceto a collection chamber by absorbing said droplet from said membranesurface.
 2. The method of claim 1, wherein each of said at least onedroplet is directed from said membrane surface by at least one rib. 3.The method of claim 1, wherein each of said at least one droplet isdirected from said membrane by an absorbent for said liquid sample. 4.The method of claim 1, further comprising providing a collection chamberfor said plurality of filtrates, and providing means in said collectionchamber for directing each of said at least one droplet from saidmembrane surface.
 5. The method of claim 1, wherein each of said atleast one droplet is directed from said membrane by a plurality of pins.